The general objectives of this Hypertension SCOR program are to elucidate the role which humoral factors play in the pathogenesis, treatment and vascular complications of hypertension. The known mineralocorticoid forms of experimental and human hypertension will be characterized according to their endocrine, renal, and hemodynamic aspects. The results will be compared with those obtained in other types of hypertension whose pathogenesis is unknown such as low-renin hypertension, metacorticoid hypertension, genetic hypertension in the SHR, and human essential hypertension. We will attempt to identify new adrenal hormones which could influence hypertension in man and experimental animals and will study the hormonal receptors for angiotensin and mineralocorticoids. In addition, the mechanisms for low-renin and high-renin hypertension will be examined according to their relationship to mineralocorticoid hormones, adrenergic function, carbohydrate tolerance, fluid volume, renal function, age, race, and response to antihypertensive therapy. The development of atherosclerosis will be studied in a number of hypertensive animal models. The effects of well-known or potential risk factors such as hyperlipidemia, carbohydrate intolerance, obesity, and the renin-angiotensin status on arterial morphology, chemical composition, and metabolism, will be evaluated. Cultured vascular smooth muscle cells and microvessel preparations will be utilized to assess the influence of vasoactive agents, hormones, and antihypertensive drugs on their metabolism, and to determine the existence of vascular hormone receptors. In addition, patient populations with demonstrated high incidence of vascular complications will be studied with respect to the role of the renin-angiotensin system and other humoral factors in the development of the vascular disease. Hypertensive-diabetic patients, patients with chronic renal failure, and patients with prior myocardial infarction will be studied in this work. The studies should provide insight into the pathogenesis and complications of hypertension and may lead to better approaches for its prevention and therapy.